Researchers have identified five enzymes that are essential to the survival of a parasitic worm that infects livestock
worldwide and is a great threat to global food security. Two of these proteins are already being studied as potential
drug targets against other pathogens.

The team sequenced the genome of Haemonchus contortus, or the barber pole worm, a well-studied parasitic worm
that resides in the gut of sheep and other livestock globally. This genome could provide a comprehensive understanding
of how treatments against parasitic worms work and point to further new treatments and vaccines.

The barber pole worm or H. contortus is part of a family of gastrointestinal worms that are endemic on 100% of
farms and are estimated to cost the UK sheep industry alone more than £80 million pounds each year. H.
contortus has become resistant to all major treatments against parasitic worms, so its genome is a good model to
understand how drug resistance develops in this complex group of closely related parasites and will also reveal further
potential drug and vaccine targets.

"Our reference genome allows researchers to understand how H. contortus and other worms of this
type acquire resistance to a wide range of anthelmintics - the drugs used to treat worm infections," says Dr
James Cotton, senior author from the Wellcome Trust Sanger Institute. "Seeing a common theme of
drug resistance in this well-characterised worm is extremely important because both people and animals are reliant on
so few treatments against parasitic worms."

The team sequenced the genome of a strain of H contortus that was susceptible to all major classes of drugs
against parasitic worms. By comparing this sequence with that of worms that have acquired drug resistance, the
researchers expect to reveal a wealth of information about how and why resistance has occurred.

" Our reference genome allows researchers to understand how H. contortus and other worms of this type
acquire resistance to a wide range of anthelmintics - the drugs used to treat worm infections. "

Dr James Cotton

"The H. contortus genome provides a rich and essential platform for future research in this and
other types of parasitic worms," says Professor Neil Sargison, author from the University of Edinburgh, Royal
(Dick) School of Veterinary Studies. "With the world population set to exceed nine billion by the
year 2050, improving the security of our food supply is crucial. Getting to grips with genomes such as that of H.
contortus is our best option to tackle the issue of drug resistance and develop new drugs against parasitic worms to
address this issue."

To generate a rich source of potential vaccine and drug target candidates, the team identified a set of genes that are
more active in certain stages of the parasite life cycle and within the parasite's gut. They also identified five
metabolic chokepoints - enzymes that are essential for a parasite's survival. Two of these enzymes are already being
studies as potential drug targets; one against Mycobacterium tuberculosis and another against another type of
worm.

To discover these targets, the team determined when and where each gene is turned on or off in the cells and tissues of
H. contortus to reveal new insights into the worm's lifecycle. The result is the most extensive dataset of its
kind for any gastrointestinal worm and is expected to provide a valuable resource for future investigations.

The researchers also described the full gene repertoires for known drug target families. This gives a comprehensive
understanding of how several important treatments work against worms and begins to unravel why resistance has occurred
in these genes.

"Not only is this worm closely related to many other parasites of livestock it is also similar to
some species of worms in humans." Professor John Gilleard, joint senior author from the University of Calgary
Faculty of Veterinary Medicine. "This makes it an extremely important model parasite species for
experimental studies.

"Revealing new drug targets against H. contortus could provide much-needed new treatment opportunities against
parasitic worms in both animals and humans."

Notes to Editors

Publication details

The genome and transcriptome of Haemonchus contortus, a key model parasite for drug and vaccine discovery.

Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta,
Canada

Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, United Kingdom

Department of Infectious Diseases and Center for Tropical and Emerging Global Disease, University of Georgia,
Athens, USA

The University of Calgary

The University of Calgary is a leading Canadian university located in the nation's most enterprising city. The
university has a clear strategic direction to become one of Canada's top five research universities by 2016, where
research and innovative teaching go hand in hand, and where we fully engage the communities we both serve and lead.
This strategy is called Eyes High, inspired by the university's Gaelic motto, which translates as 'I will lift up my
eyes.'

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

Website

The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.